User login
Study Overview
Objective. To assess the safety and effectiveness of the use of epinephrine in out-of-hospital cardiac arrest patients.
Design. Randomized, double-blind placebo-controlled trial in the United Kingdom.
Setting and participants. Patients aged 16 years or older who had sustained an out-of-hospital cardiac arrest for which advanced life support was provided by trial-trained paramedics were eligible for inclusion. Exclusion criteria included apparent pregnancy, arrest from anaphylaxis or asthma, or the administration of epinephrine before the arrival of the trial-trained paramedic. In 1 of the 5 ambulance services, traumatic cardiac arrests were also excluded in accordance with local protocol.
Main outcome measures. The primary outcome was the rate of survival at 30 days. Secondary outcomes included rate of survival until hospital admission, length of stay in the hospital and intensive care unit (ICU), rates of survival at hospital discharge and at 3 months, and neurologic outcomes at hospital discharge and at 3 months.
Main results. Between December 2014 and October 2017, 10,623 patients were screened for eligibility in 5 National Health Service ambulance services in the United Kingdom. Of these, 8103 were eligible, and 8014 patients were assigned to either the epinephrine group (4015 patients) or the placebo group (3999 patients).
For the primary outcome, 130 patients (3.2%) in the epinephrine group were alive at 30 days in comparison to 94 patients (2.4%) in the placebo group (unadjusted odds ratio [OR] for survival, 1.39; 95% confidence interval [CI], 1.06-1.82; P = 0.02). The number needed to treat for a 30-day survival was 112 patients (95% CI, 63-500).
For the secondary outcomes, the epinephrine group had a higher survival until hospital admission: 947 patients (23.8%) as compared to 319 (8.0%) patients in the placebo group (unadjusted OR, 3.59). Otherwise, there were no difference between the 2 groups in the hospital and ICU LOS. There also was not a significant difference between the epinephrine group and the placebo group in the proportion of patients who survived until hospital discharge: 87 of 4007 patients (2.2%) in the epinephrine group and 74 of 3994 patients (1.9%) in the placebo group, with an unadjusted OR of 1.18 (95% CI, 0.85-1.61). Patients in the epinephrine group had a higher rate of severe neurologic impairment at discharge: 39 of 126 patients (31.0%) versus 16 of 90 patients (17.8%).
Conclusion. Among adults with out-of-hospital cardiac arrest, the use of epinephrine resulted in a higher rate of 30-day survival as compared with the use of placebo; however, there was no difference in the rate of a favorable neurologic outcome as more survivors in the epinephrine group had severe neurologic impairment.
Commentary
Epinephrine has been used as part of the resuscitation of patients with cardiac arrest since the 1960s. Epinephrine increases vasomotor tone during circulatory collapse, shunts more blood to the heart, and increases the likelihood of restoring spontaneous circulation.1 However, epinephrine also decreases microvascular blood flow and can result in long-term organ dysfunction or hypoperfusion of the heart and brain.2 The current study, the PARAMEDIC2 trial, by Perkins and colleagues is the largest randomized controlled trial to date to address the question of patient-centered benefit of the use of epinephrine during out-of-hospital cardiac arrest.
Similar to prior studies, patients who received epinephrine had a higher rate of 30-day survival than those who received placebo. However, there was no clear improvement in functional recovery among patients who survived, and the proportion of survivors with severe neurologic impairment was higher in the epinephrine group as compared to the placebo group. These results demonstrate that despite its ability to restore spontaneous circulation after out-of-hospital cardiac arrest, epinephrine produced only a small absolute increase in survival with worse functional recovery as compared with placebo.
One major limitation of this study is that the protocol did not control for or measure in-hospital treatments. In a prior study, the most common cause of in-hospital death was iatrogenic limitation of life support, which may result in the death of potentially viable patients.3 Another limitation of the study was the timing to administration of epinephrine. In the current study, paramedics administered the trial agent within a median of 21 minutes after the emergency call, which is a longer duration than previous out-of-hospital trials.4 In addition, this time to administration is much longer than that of in-hospital cardiac arrest, where epinephrine is administered a median of 3 minutes after resuscitation starts.5 Therefore, the results from this study cannot be extrapolated to patients with in-hospital cardiac arrest.
Applications for Clinical Practice
The current study by Perkins et al demonstrated the powerful effect of epinephrine in restoring spontaneous circulation after out-of-hospital cardiac arrest. However, epinephrine produced only a small absolute increase in survival with worse functional recovery, as compared to placebo. While further studies regarding dosage of epinephrine as well as administration based on the basis of cardiac rhythm are needed, we should question our tradition of using epinephrine in out-of-hospital cardiac arrest if meaningful neurological function is our priority.
—Ka Ming Gordon Ngai, MD, MPH, FACEP
1. Paradis NA, Martin GB, Rosenberg J, et al. The effect of standard- ad high-dose epinephrine on coronary perfusion pressure during prolonged cardiopulmonary resuscitation. JAMA. 1991;265:1139-1144.
2. Ristagno G, Sun S, Tang W, et al. Effects of epinephrine and vasopressin on cerebral microcirculatory flows during and after cardiopulmonary resuscitation. Crit Care Med. 2007;35:2145-2149.
3. Elmer J, Torres C, Aufderheide TP, et al. Association of early withdrawal of life-sustaining therapy for perceived neurological prognosis with mortality after cardiac arrest. Resuscitation. 2016;102:127-135.
4. Kudenchuk PJ, Brown SP, Daya M, et al. Amiodarone, lidocaine, or placebo in out-of-hospital cardiac arrest. N Engl J Med. 2016;374:1711-1722.
5. Donnino MW, Salciccioli JD, Howell MD, et al. Time to administration of epinephrine and outcome after in-hospital cardiac arrest with non-shockable rhythms: retrospective analysis of large in-hospital data registry. BMJ. 2014;348:g3028l.
Study Overview
Objective. To assess the safety and effectiveness of the use of epinephrine in out-of-hospital cardiac arrest patients.
Design. Randomized, double-blind placebo-controlled trial in the United Kingdom.
Setting and participants. Patients aged 16 years or older who had sustained an out-of-hospital cardiac arrest for which advanced life support was provided by trial-trained paramedics were eligible for inclusion. Exclusion criteria included apparent pregnancy, arrest from anaphylaxis or asthma, or the administration of epinephrine before the arrival of the trial-trained paramedic. In 1 of the 5 ambulance services, traumatic cardiac arrests were also excluded in accordance with local protocol.
Main outcome measures. The primary outcome was the rate of survival at 30 days. Secondary outcomes included rate of survival until hospital admission, length of stay in the hospital and intensive care unit (ICU), rates of survival at hospital discharge and at 3 months, and neurologic outcomes at hospital discharge and at 3 months.
Main results. Between December 2014 and October 2017, 10,623 patients were screened for eligibility in 5 National Health Service ambulance services in the United Kingdom. Of these, 8103 were eligible, and 8014 patients were assigned to either the epinephrine group (4015 patients) or the placebo group (3999 patients).
For the primary outcome, 130 patients (3.2%) in the epinephrine group were alive at 30 days in comparison to 94 patients (2.4%) in the placebo group (unadjusted odds ratio [OR] for survival, 1.39; 95% confidence interval [CI], 1.06-1.82; P = 0.02). The number needed to treat for a 30-day survival was 112 patients (95% CI, 63-500).
For the secondary outcomes, the epinephrine group had a higher survival until hospital admission: 947 patients (23.8%) as compared to 319 (8.0%) patients in the placebo group (unadjusted OR, 3.59). Otherwise, there were no difference between the 2 groups in the hospital and ICU LOS. There also was not a significant difference between the epinephrine group and the placebo group in the proportion of patients who survived until hospital discharge: 87 of 4007 patients (2.2%) in the epinephrine group and 74 of 3994 patients (1.9%) in the placebo group, with an unadjusted OR of 1.18 (95% CI, 0.85-1.61). Patients in the epinephrine group had a higher rate of severe neurologic impairment at discharge: 39 of 126 patients (31.0%) versus 16 of 90 patients (17.8%).
Conclusion. Among adults with out-of-hospital cardiac arrest, the use of epinephrine resulted in a higher rate of 30-day survival as compared with the use of placebo; however, there was no difference in the rate of a favorable neurologic outcome as more survivors in the epinephrine group had severe neurologic impairment.
Commentary
Epinephrine has been used as part of the resuscitation of patients with cardiac arrest since the 1960s. Epinephrine increases vasomotor tone during circulatory collapse, shunts more blood to the heart, and increases the likelihood of restoring spontaneous circulation.1 However, epinephrine also decreases microvascular blood flow and can result in long-term organ dysfunction or hypoperfusion of the heart and brain.2 The current study, the PARAMEDIC2 trial, by Perkins and colleagues is the largest randomized controlled trial to date to address the question of patient-centered benefit of the use of epinephrine during out-of-hospital cardiac arrest.
Similar to prior studies, patients who received epinephrine had a higher rate of 30-day survival than those who received placebo. However, there was no clear improvement in functional recovery among patients who survived, and the proportion of survivors with severe neurologic impairment was higher in the epinephrine group as compared to the placebo group. These results demonstrate that despite its ability to restore spontaneous circulation after out-of-hospital cardiac arrest, epinephrine produced only a small absolute increase in survival with worse functional recovery as compared with placebo.
One major limitation of this study is that the protocol did not control for or measure in-hospital treatments. In a prior study, the most common cause of in-hospital death was iatrogenic limitation of life support, which may result in the death of potentially viable patients.3 Another limitation of the study was the timing to administration of epinephrine. In the current study, paramedics administered the trial agent within a median of 21 minutes after the emergency call, which is a longer duration than previous out-of-hospital trials.4 In addition, this time to administration is much longer than that of in-hospital cardiac arrest, where epinephrine is administered a median of 3 minutes after resuscitation starts.5 Therefore, the results from this study cannot be extrapolated to patients with in-hospital cardiac arrest.
Applications for Clinical Practice
The current study by Perkins et al demonstrated the powerful effect of epinephrine in restoring spontaneous circulation after out-of-hospital cardiac arrest. However, epinephrine produced only a small absolute increase in survival with worse functional recovery, as compared to placebo. While further studies regarding dosage of epinephrine as well as administration based on the basis of cardiac rhythm are needed, we should question our tradition of using epinephrine in out-of-hospital cardiac arrest if meaningful neurological function is our priority.
—Ka Ming Gordon Ngai, MD, MPH, FACEP
Study Overview
Objective. To assess the safety and effectiveness of the use of epinephrine in out-of-hospital cardiac arrest patients.
Design. Randomized, double-blind placebo-controlled trial in the United Kingdom.
Setting and participants. Patients aged 16 years or older who had sustained an out-of-hospital cardiac arrest for which advanced life support was provided by trial-trained paramedics were eligible for inclusion. Exclusion criteria included apparent pregnancy, arrest from anaphylaxis or asthma, or the administration of epinephrine before the arrival of the trial-trained paramedic. In 1 of the 5 ambulance services, traumatic cardiac arrests were also excluded in accordance with local protocol.
Main outcome measures. The primary outcome was the rate of survival at 30 days. Secondary outcomes included rate of survival until hospital admission, length of stay in the hospital and intensive care unit (ICU), rates of survival at hospital discharge and at 3 months, and neurologic outcomes at hospital discharge and at 3 months.
Main results. Between December 2014 and October 2017, 10,623 patients were screened for eligibility in 5 National Health Service ambulance services in the United Kingdom. Of these, 8103 were eligible, and 8014 patients were assigned to either the epinephrine group (4015 patients) or the placebo group (3999 patients).
For the primary outcome, 130 patients (3.2%) in the epinephrine group were alive at 30 days in comparison to 94 patients (2.4%) in the placebo group (unadjusted odds ratio [OR] for survival, 1.39; 95% confidence interval [CI], 1.06-1.82; P = 0.02). The number needed to treat for a 30-day survival was 112 patients (95% CI, 63-500).
For the secondary outcomes, the epinephrine group had a higher survival until hospital admission: 947 patients (23.8%) as compared to 319 (8.0%) patients in the placebo group (unadjusted OR, 3.59). Otherwise, there were no difference between the 2 groups in the hospital and ICU LOS. There also was not a significant difference between the epinephrine group and the placebo group in the proportion of patients who survived until hospital discharge: 87 of 4007 patients (2.2%) in the epinephrine group and 74 of 3994 patients (1.9%) in the placebo group, with an unadjusted OR of 1.18 (95% CI, 0.85-1.61). Patients in the epinephrine group had a higher rate of severe neurologic impairment at discharge: 39 of 126 patients (31.0%) versus 16 of 90 patients (17.8%).
Conclusion. Among adults with out-of-hospital cardiac arrest, the use of epinephrine resulted in a higher rate of 30-day survival as compared with the use of placebo; however, there was no difference in the rate of a favorable neurologic outcome as more survivors in the epinephrine group had severe neurologic impairment.
Commentary
Epinephrine has been used as part of the resuscitation of patients with cardiac arrest since the 1960s. Epinephrine increases vasomotor tone during circulatory collapse, shunts more blood to the heart, and increases the likelihood of restoring spontaneous circulation.1 However, epinephrine also decreases microvascular blood flow and can result in long-term organ dysfunction or hypoperfusion of the heart and brain.2 The current study, the PARAMEDIC2 trial, by Perkins and colleagues is the largest randomized controlled trial to date to address the question of patient-centered benefit of the use of epinephrine during out-of-hospital cardiac arrest.
Similar to prior studies, patients who received epinephrine had a higher rate of 30-day survival than those who received placebo. However, there was no clear improvement in functional recovery among patients who survived, and the proportion of survivors with severe neurologic impairment was higher in the epinephrine group as compared to the placebo group. These results demonstrate that despite its ability to restore spontaneous circulation after out-of-hospital cardiac arrest, epinephrine produced only a small absolute increase in survival with worse functional recovery as compared with placebo.
One major limitation of this study is that the protocol did not control for or measure in-hospital treatments. In a prior study, the most common cause of in-hospital death was iatrogenic limitation of life support, which may result in the death of potentially viable patients.3 Another limitation of the study was the timing to administration of epinephrine. In the current study, paramedics administered the trial agent within a median of 21 minutes after the emergency call, which is a longer duration than previous out-of-hospital trials.4 In addition, this time to administration is much longer than that of in-hospital cardiac arrest, where epinephrine is administered a median of 3 minutes after resuscitation starts.5 Therefore, the results from this study cannot be extrapolated to patients with in-hospital cardiac arrest.
Applications for Clinical Practice
The current study by Perkins et al demonstrated the powerful effect of epinephrine in restoring spontaneous circulation after out-of-hospital cardiac arrest. However, epinephrine produced only a small absolute increase in survival with worse functional recovery, as compared to placebo. While further studies regarding dosage of epinephrine as well as administration based on the basis of cardiac rhythm are needed, we should question our tradition of using epinephrine in out-of-hospital cardiac arrest if meaningful neurological function is our priority.
—Ka Ming Gordon Ngai, MD, MPH, FACEP
1. Paradis NA, Martin GB, Rosenberg J, et al. The effect of standard- ad high-dose epinephrine on coronary perfusion pressure during prolonged cardiopulmonary resuscitation. JAMA. 1991;265:1139-1144.
2. Ristagno G, Sun S, Tang W, et al. Effects of epinephrine and vasopressin on cerebral microcirculatory flows during and after cardiopulmonary resuscitation. Crit Care Med. 2007;35:2145-2149.
3. Elmer J, Torres C, Aufderheide TP, et al. Association of early withdrawal of life-sustaining therapy for perceived neurological prognosis with mortality after cardiac arrest. Resuscitation. 2016;102:127-135.
4. Kudenchuk PJ, Brown SP, Daya M, et al. Amiodarone, lidocaine, or placebo in out-of-hospital cardiac arrest. N Engl J Med. 2016;374:1711-1722.
5. Donnino MW, Salciccioli JD, Howell MD, et al. Time to administration of epinephrine and outcome after in-hospital cardiac arrest with non-shockable rhythms: retrospective analysis of large in-hospital data registry. BMJ. 2014;348:g3028l.
1. Paradis NA, Martin GB, Rosenberg J, et al. The effect of standard- ad high-dose epinephrine on coronary perfusion pressure during prolonged cardiopulmonary resuscitation. JAMA. 1991;265:1139-1144.
2. Ristagno G, Sun S, Tang W, et al. Effects of epinephrine and vasopressin on cerebral microcirculatory flows during and after cardiopulmonary resuscitation. Crit Care Med. 2007;35:2145-2149.
3. Elmer J, Torres C, Aufderheide TP, et al. Association of early withdrawal of life-sustaining therapy for perceived neurological prognosis with mortality after cardiac arrest. Resuscitation. 2016;102:127-135.
4. Kudenchuk PJ, Brown SP, Daya M, et al. Amiodarone, lidocaine, or placebo in out-of-hospital cardiac arrest. N Engl J Med. 2016;374:1711-1722.
5. Donnino MW, Salciccioli JD, Howell MD, et al. Time to administration of epinephrine and outcome after in-hospital cardiac arrest with non-shockable rhythms: retrospective analysis of large in-hospital data registry. BMJ. 2014;348:g3028l.